The University of Newcastle, Australia

The mysteries of sperm function

Tenacious and audacious in equal measure, Associate Professor Mark Baker is seeking to crack the genetic code of male infertility.

Mark BakerDiagnosing male factor infertility – which accounts for half of all Assisted Reproduction Technologies (ART) procedures in Australia – is akin to solving a 5000 odd-piece jigsaw puzzle. Some pieces or answers, like reduced sperm number and motility, are right in front of you; they're big and obvious, and usually the first to be picked up and put down by novice game players. They frame the puzzle and make it easier to work inward. Then there are some pieces, like genetic differences, that are much smaller in size or even hidden; they're not your typical go-tos and they're not easy to place. But they are necessary to complete the picture.

Associate Professor Mark Baker, touted as a pioneer of sperm proteomics, is leading worldwide efforts to explore and understand the latter.

I study the structure and function of proteomes

"These are the entire sets of proteins that are expressed by genomes."

The professional researcher, who was awarded a National Health and Medical Research Council Career Development Fellowship in early 2012, uses mass spectrometry to illustrate the chemical composition of larger molecules and cells. Spanning the life sciences, medicine and engineering arenas, this work is housed in a state-of-the-art laboratory at the University of Newcastle.

"The implications of our research are widespread," Mark affirms.

"About 1 in 15 men are infertile."

"Medicare-funded statistics point to an IVF success rate of just 22 per cent, which is equally concerning."

"It's important we develop more efficient and effective ways of finding the best sperm."

Divide and conquer

Taking a "roundabout route" to get to this point, Mark began his research career in the cancer field. The energetic educator and innovator undertook a PhD at Melbourne's Monash University in 1999, principally using it to investigate the relationship between chemotherapy and cell death.

"We wanted to look at what the chemical treatment is doing to the body," he asserts.

"It's basically a poison."

Seeking to gain a more intricate understanding of the cell cycle during his three-year probe, Mark closely observed the mechanism by which microscopic units were dying during the chemotherapy process.

"Cells that are dividing are more susceptible to cell death than cells that aren't dividing," he explains.

"Cancers can be destroyed as the cells die, but that happens to be how people lose their hair and the lining of the stomach as well."

Back to basics

Mark relocated to Newcastle after his PhD was conferred in 2002, linking up with Laureate Professor John Aitkin and the University's influential Reproductive Science Group. Inspired by new technologies at the time, the creative collaborator looked to put an unusual twist on his PhD theme.

"Proteomics allowed us to compare the difference between normal biological cells and cancer cells," he states.

"We can do the same thing with male reproductive cells - compare the difference between those belonging to fertile men and those belonging to infertile men and find out what's missing."

"It's a fascinating question."

From 2002-2011, Mark also undertook some basic science research on the behaviours and movement patterns of sperm. This time exploring the differences between mature cells and immature cells, the expert sought to understand the "hows" and "whys" of their storage and travel.

"We found that a sperm is immotile in the testes and cannot recognise the egg until it reaches the bottom of the epididymis," he illuminates.

"We found that immature sperm undergo changes in their phosphorylation status too."

"Some of the motor proteins become 'oiled' and this enables the tail to become motile, which is necessary for fertilisation."

"Essentially, the whole head and surface of the sperm are remodelled from the early regions to the later regions."

Spot the difference

Still endeavouring to define the differences between the sperm of fertile men and the sperm of infertile men, Mark is aiming to one day soon diagnose and prognose 80-90% of male infertility cases.  Working on the proviso that "the more cases looked at, the more that is found," the ambitious academic is in the process of analysing more than 100 samples locked away in his laboratory. 

"At the moment we can probably detect 30%," he declares.

"Some of the guys are missing proteins in the head area, which means they're unable to recognise and bind with the egg."

"Others are missing a protein in the neck area, so the head and tail actually fall apart over a period of time."

"Proteins in the tail area are stopping the sperm from being normally motile as well."

Believing such patterns will "become repetitive" with enough data, Mark is hoping to have a diagnostic framework completed in 2-3 years' time.

"The hardest thing for us is obtaining donations," he acknowledges.

"At the moment, we've had to go to Brazil."

"We need interested, local men to come forward."

"Within a week we can do five samples and determine what's missing within them, so it doesn't take very long."

At the same time, Mark is collaborating with neurology expert Dr Neil Spratt on a clinical stroke research project. Again attempting to figure out the "whys" behind the "what is," the duo is seeking to compare the difference between normal cerebral spinal fluid and cerebral spinal fluid that belongs to patients who've had a "minor stroke."

"In a period of 24 hours while they're recovering, the latter group will often have another, more major stroke," the reproductive scientist elucidates.

"It's killing a lot of people."

Already identifying a handful of molecules responsible for causing the second, lethal stroke, the pair is eager to move on to the prevention stage and develop a number of single-targeted inhibitors.

Changing tactics for changing times

Keen to move past mere motility and morphology when it comes to analysing semen samples, Mark is pushing for big transformations in the way suspected infertilities are investigated in Australia. The University of Newcastle Research Fellow has been doing so since he made the switch to translational research in 2012.

"Females have to undergo invasive laparoscopies and pelvic examinations," he reveals.

"We want the focus to go instantly to the male."

"It's so easy to get an ejaculate and bring it to the lab."

"Within an hour we can have a diagnosis as to whether the couple can conceive or not."